The winding path of protein methylation research: milestones and new frontiers

Abstract

In 1959, while analysing the bacterial flagellar proteins, Ambler and Rees observed an unknown species of amino acid that they eventually identified as methylated lysine. Over half a century later, protein methylation is known to have a regulatory role in many essential cellular processes that range from gene transcription to signal transduction. However, the road to this now burgeoning research field was obstacle-ridden, not least because of the inconspicuous nature of the methyl mark itself. Here, we chronicle the milestone achievements and discuss the future of protein methylation research.

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Figure 1: Milestones in protein methylation research.
Figure 2: Interfaces between protein methylation and biological processes.
Figure 3: Protein methylation in numbers.

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Acknowledgements

The authors thank L. Sawyer for help with retrieving information and materials relating to Richard Ambler's research; P. Hornbeck for help with the analyses of known methylated proteins; O. Gozani, J. Olsen and B. Fischer for discussions; and M. Teplova for help with the figures. Work in the laboratory of Y.S. is supported by the US National Institutes of Health (CA118487, GM117264 and MH096066) and Boston Children's Hospital. Y.S. is an American Cancer Society Research Professor. The authors apologize to colleagues whose work could not be cited owing to space limitations.

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Correspondence to Jernej Murn or Yang Shi.

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Y.S. is a co-founder of Constellation Pharmaceuticals, Inc., Cambridge, Massachusetts, USA, and is a member of its scientific advisory board. Y.S. is also a consultant for Active Motif, Carlsbad, California, USA.

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Murn, J., Shi, Y. The winding path of protein methylation research: milestones and new frontiers. Nat Rev Mol Cell Biol 18, 517–527 (2017). https://doi.org/10.1038/nrm.2017.35

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